73 articles - From Friday May 20 2022 to Friday May 27 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
| Blood Adv |
Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis. Results were consistent in patients with cirrhosis, solid cancer, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent non-malignant risk factors. In patients with SVT the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti-spike neutralizing IgG to SARS-CoV-2 variants, but preserved antigen-specific T cell responses. All cohorts had functional T cell responses. Median anti-spike IgG decreased 4-fold from second to third dose (p=0.004). Only 5/29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant. |
| Blood |
A core group of structurally similar HLA-DPB1 alleles drives permissiveness after hematopoietic cell transplantation. In a CIBMTR cohort of 5140 10/10-matched patients transplanted for AML, ALL, or MDS from 2008-2017, the risks of aGVHD II-IV increased progressively from "core" TCE3 permissive (N=930; HR 1.12 [0.98-1.28]; p=0.1012) to "non-core" TCE3-permissive (N=1286; HR 1.24 [1.06-1.46]; p= 0.0082), and non-permissive mismatches (N=2023; HR 1.32 [1.16-1.50]; p<.0001) compared to allele-matched patients (N=785). "Core" TCE3-permissive pairs (HR 0.78 [0.68-0.88]; p=0.0002), but not "non-core" TCE3-permissive pairs (HR 0.95 [0.83-1.09]; p=0.4578) showed significantly lower risks of TRM when compared to non-permissive pairs. Our results suggest that frequent mismatches between structurally similar "core" HLA-DPB1 alleles are the main drivers of permissiveness after HCT, and provide evidence for a role of immunopeptidome differences between mismatched HLA-DPB1 alleles in the clinical outcome of HCT. |
CD19/22 CAR T-cells in Children and Young Adults with B-ALL: Phase I Results and Development of a Novel Bicistronic CAR. With demonstrated safety and efficacy of CD19.22. BBz in a heavily pre-treated CAYA B-ALL cohort, further optimization of combinatorial antigen targeting serves to overcome identified limitations. ( NCT03448393). |
Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. A population-based logistic growth model indicated slower MRD median doubling time post-EOT with venetoclax-rituximab (93 days) vs bendamustine-rituximab (53 days; P = 1.2 x 10-7). No new safety signals were identified. Sustained survival, uMRD benefits and durable responses support 2-year fixed-duration venetoclax-rituximab treatment in R/R CLL. |
Inherited bone marrow failure in the pediatric patient. Management of some of the other complications, such as cancer, remains a challenge. Recent studies suggest the possibility of new and potentially more efficacious therapies. This includes renewed focus on hematopoietic gene therapy and drugs (TGF-b inhibitors for FA and PAPD5 inhibitors for DC) that target disease specific defects. |
NOTCH1 signaling during CD4+ T-cell activation alters transcription factor networks and enhances antigen responsiveness. NOTCH1-agonized CD4+ CAR-T demonstrated enhanced antigen responsiveness and proliferated to strikingly higher frequencies in mice bearing human lymphoma xenografts. NOTCH1-agonized CD4+ CAR-T also provided superior help to co-transferred CD8+ CAR-T, driving improved expansion and curative anti-tumor responses in vivo at low CAR-T doses. Our data expand the mechanisms by which NOTCH can shape CD4+ T-cell behavior and demonstrate that activating NOTCH1 signaling during genetic modification ex vivo is a potential strategy for enhancing the function of T-cells engineered with tumor-targeting receptors. |
Patients with CLL have lower risk of death from COVID-19 in the omicron era. In a cohort of patients with CLL tested for severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) at hospital test sites in the time periods before and after dominance of the omicron variant, rates of hospitalizations and ICU-admissions declined significantly, whereas 30-day mortality remained as high as 23% in the period with dominance of the omicron sublineage BA.2 variant. However, for a larger population-based cohort of patients with CLL (including the hospital cohort), 30-day mortality was 2%. Thus, patients with CLL with close hospital contacts and in particular those above 70 years of age with one or more comorbidities should be considered for closer monitoring and pre-emptive antiviral therapy upon a positive SARS-CoV-2 test. |
Revisiting anemia in sickle cell disease and finding the balance with therapeutic approaches. However, although anemia is clearly associated with many detrimental outcomes, it may also have an advantage in SCD in lowering risks of potential viscosity-related complications. Until recently, clinical drug development for SCD has predominantly targeted a reduction in the frequency of vaso-occlusive crises as an endpoint, but increasingly, more attention is being directed toward addressing the contribution of chronic anemia to poor outcomes in SCD. This article aims to explore the complex pathophysiology and mechanisms of anemia in SCD, as well as the need to balance the benefits of raising hemoglobin levels with the potential risks of increasing blood viscosity, in the context of the current therapeutic landscape for anemia in SCD. |
The multifaceted role of platelets in mediating brain function. In this review we outline the broad repertoire of platelet function in the central nervous system, focusing on the similarities between platelets and neurons. We also summarize the role that platelets play in the pathophysiology of various neurological diseases, with a particular focus on neuroinflammation and neurodegeneration. Finally, we highlight the exciting prospect of harnessing the unique features of the platelet proteome and extracellular vesicles, which are rich in neurotrophic, anti-oxidative and anti-inflammatory factors, for the development of novel neuroprotective and neuroregenerative interventions to treat various neurodegenerative and traumatic pathologies. |
| Blood Adv |
Depth of response and response kinetics of isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma. Exploratory analysis indicates that both current CR and MRD-negative CR rates are underestimated due to M-protein interference (potential adjusted CR rate: 45.8%; potential adjusted MRD-negative CR rate: 24.0%) In conclusionthere was a clinically meaningful improvement in depth of response with Isa-Kd. CR rate in Isa-Kd was 39.7%. Mass spectrometry suggests that the potential adjusted CR rate could reach an unprecedented 45.8% of patients treated in Isa-Kd. |
Dominant epitopes presented by prevalent HLA alleles permit wide use of banked CMVpp65 T-cells in adoptive therapy. All dominant CMVpp65CTLs exhibited HLA-restricted cytotoxicity against epitope loaded targets, and usually cleared CMV infections. However, immunodominant CMVpp65 CTL responding to epitopes presented by certain HLA B*35 alleles were ineffective in lysing CMV infected cells in vitro or controlling CMV infections post adoptive therapy. Analysis of the hierarchy of T-cell responses to CMVpp65, the HLA alleles presenting immunodominant CMVpp65 epitopes, and the responses they induce, may lead to detailed algorithms for optimal choice of 3rd party CMVpp65CTLs for effective adoptive therapy. |
HLA-Matching with PTCy: A Reanalysis of a CIBMTR Dataset with Propensity Score Matching and Donor Age. After stratification by conditioning intensity, MUD BMTs in the RIC cohort had a lower risk of NRM (HR, 0.56 [0.14-0.99], P=0.05), with no significant difference in other clinical outcomes. These results suggest that the effect of HLA matching on BMT outcomes with PTCy is less meaningful than previously reported and observed differences resulted in part from differences in donor age. Timely identification of a young, at least half-matched (related or unrelated) donor may be more important than finding a matched donor, if the latter leads to a substantial delay in BMT or use of an older donor. |
Impact of the MRD status in AML patients undergoing allogeneic stem cell transplantation in first vs second remission. Noteworthy, MRDpos patients transplanted in first remission and MRDneg patients transplanted in second remission had similar outcomes. In the clinically highly relevant group of ELN2017 intermediate risk individuals, the MRD status provided the highest prognostic value with very dismal outcomes of patients transplanted in MRDpos second remission. The adverse outcomes of MRDpos patients and individuals transplanted in second remission should be considered when planning consolidation treatment, to avert an allogeneic HSCT in MRDpos second remission when possible. |
Latent Membrane Proteins from EBV Differentially Target Cellular Pathways to Accelerate MYC-induced Lymphomagenesis. Interestingly, p53 mutations were less observed in LMP1-expressing BL although they were not significantly changed by EBV infection, indicating LMP1 may lessen p53 mutations in human primary BL. This suggests LMP1 effects in EBV-associated human BL varies from what we observe in our murine model. Finally our studies suggest a novel pathogenic role of LMP1 in lymphomagenesis. |
Lower-leg injury and knee arthroscopy have distinct effects on coagulation. After knee arthroscopy, plasma levels of al parameters decreased. Lower-leg trauma is associated with increased procoagulant factor levels, in contrast to knee arthroscopy. This finding suggests that in both situations, different pathways are involved in development of VTE. |
PNMZL and PTFL: morphological variants with a common molecular profile - a unifying hypothesis. Genetic alterations typically seen in conventional NMZL, were absent in PNMZL. In summary, overlapping clinical, morphological and molecular findings including low genetic complexity, recurrent alterations in MAP2K1, TNFRSF14 and IRF8, and similar methylation profiles indicate that PNMZL and PTFL are likely part of a single disease with variation in the histological spectrum. The term "pediatric-type follicular lymphoma with and without marginal zone differentiation" is suggested. |
The clinical and laboratory diagnosis of vaccine-induced immune thrombotic thrombocytopenia. These immunoassays had specificities of 95.6% [95% confidence interval (CI) 90.0-98.6], 96.5% (95% CI 91.2-99.0), and 97.4% (95% CI 92.4-99.5), respectively. Functional tests, including the standard SRA and PF4/heparin-SRA, had high specificities (100%), but poor sensitivities for VITT [16.7% (95% CI 7.0-31.4); and 46.2% (95% CI 26.6-66.6), respectively]. These findings suggest EIA assays that can directly detect antibodies to PF4 or PF4/heparin have excellent performance characteristics and may be useful as a diagnostic test if the PF4-SRA is unavailable. |
| Blood Cancer J |
Improved trends in survival and engraftment after single cord blood transplantation for adult acute myeloid leukemia. The improved OS among patients in = complete remission (CR)3 and active disease at CBT was mainly due to a reduction of relapse-related mortality, whereas among patients in first or second CR at CBT, this was due mainly to a reduction of non-relapse mortality. The trends of neutrophil engraftment also improved over time. This experience demonstrated that the survival and engraftment rate after CBT for this group has improved over the past 22 years. |
Pirtobrutinib inhibits wild-type and mutant Bruton's tyrosine kinase-mediated signaling in chronic lymphocytic leukemia. Both chemokines were decreased at early time points and mimicked BCR pathway protein changes. Collectively, these results demonstrate that pirtobrutinib is an effective BTK inhibitor for CLL harboring wild-type or mutant BTK as observed by changes in CCL3 and CCL4 biomarkers and suggest that alterations in BCR pathway signaling are the mechanism for its clinical effects. Long-term evaluation is needed for BTK gatekeeper residue variation along with pathologic kinase substitution or mutations in other proteins in the BCR pathway. |
| Haematologica |
Comparable long-term outcomes between upfront haploidentical and identical sibling donor transplant in aplastic anemia: a national registry-based study. Physical and mental component summaries in adults as well as physical, mental, social, and role well-being in children were al similar between HID and ISD SCT at 5-year points. At the last followup, the proportion of returning to society was comparable between the HID and ISD groups, showing 78.0% versus 84.6% among children and 74.6% versus 81.2% among adults. These data suggest that haploidentical transplant can be considered a potential therapeutic option in the upfront setting for SAA patients in the absence of an HLA identical related or unrelated donor. |
Durable discontinuation of systemic therapy in patients affected by chronic graft versus host disease. peripheral blood) as a graft source were associated with a greater likelihood of ST discontinuation. Although a minority of patients can discontinue systemic treatment permanently, most patients require prolonged systemic treatment. Viewing chronic GVHD in this way has implications for management approaches. |
Inhibition of DAGLß as a therapeutic target for pain in sickle cell disease. Systemic and intraplantar administration of KT109, an inhibitor of DAGLß, decreased mechanical and heat hyperalgesia in HbSS mice. The decrease in hyperalgesia was accompanied by reductions in 2-AG, PGE2 and PGE2-G in the blood. These results indicate that maintaining the physiological level of 2-AG in the blood by targeting DAGLß may be a novel and effective approach to treat pain in SCD. |
Kinetics of early and late molecular recurrences after first-line imatinib cessation in chronic myeloid leukemia: updated results from the STIM2 trial. Imatinib treatment and deep molecular response durations and BCR::ABL1/ABL1 levels at TKI cessation as quantified by RT-ddPCR are involved in MRec occurring up to 24 months but not beyond. (ClinicalTrial. gov Identifier NCT#0134373). |
Regulation of Human T-cell Leukemia Virus type 1 antisense promoter by Myocyte Enhancer Factor-2C in the context of Adult T-cell leukemia and lymphoma. High enrichment of MEF-2C was observed at the 3'LTR along with cofactors Menin and JunD resulting in binding of MEF-2C to HBZ at this region. Chemical inhibition of MEF-2 proteins resulted in the cytotoxicity of ATLL cells in vitro and reduction of proviral load in humanized mouse model. Taken together, this study provides a novel mechanism of 3'LTR regulation and establishes MEF-2 signaling a potential target for therapeutic intervention for ATLL. |
Schlafen2 is a regulator of quiescence in adult murine hematopoietic stem cells. This additionally caused an increased amount of apoptotic stem and progenitor cells. Taken together, our findings demonstrate that dysregulation of Slfn2 results in a functional deficiency of primitive hematopoietic cells, which is particularly reflected by a drastically impaired ability to reconstitute the hematopoietic system following transplantation and an increase in HSC proliferation. This study thus i dentifies S lfn2 as a n ov el a nd critical regulator of a dult H SCs and HSC quiescence. |
| J Hematol Oncol |
Safety of two-dose COVID-19 vaccination (BNT162b2 and CoronaVac) in adults with cancer: a territory-wide cohort study. In this territory-wide cohort study of patients with cancer, the incidence of AESI following vaccination with two doses of either BNT162b2 or CoronaVac vaccines was low. The findings of this study can reassure clinicians and patients with cancer about the overall safety of BNT162b2 and CoronaVac in patients with cancer, which could increase the COVID-19 vaccination rate in this vulnerable group of patients. |
| Lancet Haematol |
Ruxolitinib versus best available therapy in inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): 5-year follow up of a randomised, phase 3b study. No treatment-related deaths occurred during the study. Interpretation 5-year results from the RESPONSE-2 study support the use of ruxolitinib as a second-line therapy of choice for patients with inadequately controlled polycythaemia vera without splenomegaly. Funding Novartis. |
Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial. Vector derived FIX:C concentration is sufficiently high to prevent bleeding events and minimise the need for replacement therapy in small populations with haemophilia B. These findings support further study. Funding Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences, National Key Research and Development Program of China, National Natural Science Foundation of China, Tianjin Municipal Science and Technology Commission Grant, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. |
| Leukemia |
An N-glycosylation hotspot in immunoglobulin Here, we exploited LC sequence information from previously published amyloidogenic and control clonal LCs and from a series of 220 patients with AL amyloidosis or multiple myeloma followed at our Institutions to define sequence and spatial features of N-glycosylation, combining bioinformatics, biochemical, proteomics, structural and genetic analyses. We found peculiar sequence and spatial pattern of N-glycosylation in amyloidogenic |
Inability to phosphorylate Y88 of p27Kip1 enforces reduced p27 protein levels and accelerates leukemia progression. This was accompanied by a robust reduction of p27-Y88F levels in v-ABL transformed cells. Reduced p27-Y88F levels seem to be required for efficient cell proliferation and may subsequently support accelerated leukemia progression. The potent downregulation p27-Y88F levels in al leukemia-derived cells could uncover a novel mechanism in human oncogenesis, where reduced p27 levels are frequently observed. |
PU.1 and MYC transcriptional network defines synergistic drug responses to KIT and LSD1 inhibition in acute myeloid leukemia. Using a live cell biosensor for AKT activity, we identify early adaptive changes in kinase signaling following KIT inhibition that are reversed with the addition of LSD1 inhibitor via modulation of the GSK3a/b axis. Multi-omic analyses, including scRNA-seq, ATAC-seq and CUT&Tag, confirm these mechanisms in primary KIT-mutant AML. Collectively, this work provides rational for a clinical trial to assess the efficacy of KIT and LSD1 inhibition in patients with KIT-mutant AML. |
Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study. The percentage of EUTOS reference laboratories (n |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer. ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST. |
| Blood |
| J Hematol Oncol |
The potential role of N7-methylguanosine (m7G) in cancer. Increasing evidence indicates a critical role for m7G in human disease development, especially cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. Currently, the underlying molecular mechanisms of m7G modification in cancer are not comprehensively understood. Here, we review the current knowledge regarding the potential function of m7G modifications in cancer and discuss future m7G-related diagnostic and therapeutic strategies. |
Worked to the bone: antibody-based conditioning as the future of transplant biology. Most antibody-based conditioning therapies involve monoclonal/naked antibodies, such as alemtuzumab for graft-versus-host disease prophylaxis and rituximab for Epstein-Barr virus prophylaxis, which are both in Phase II trials for inclusion in conditioning regimens. Nevertheless, alternative immune-based therapies, including antibody-drug conjugates, radio-labelled antibodies and CAR-T cells, are showing promise in a conditioning setting. Here, we analyse the current status of antibody-based drugs in pre-transplant conditioning regimens and assess their potential in the future of transplant biology. |
| Leukemia |
Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: the 2022 update of the recommendations by ERIC, the European Research Initiative on CLL. Recommendations for robust immunogenetic analysis exist thanks to dedicated efforts by ERIC, the European Research Initiative on CLL, covering al test phases, from the pre-analytical and analytical to the post-analytical, pertaining to the analysis, interpretation, and reporting of the findings. That said, these recommendations apply to Sanger sequencing, which is increasingly being superseded by next generation sequencing (NGS), further underscoring the need for an update. Here, we present an overview of the clinical utility of immunogenetics in CLL and update our analytical recommendations with the aim to assist in the refined management of patients with CLL. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Cancer J |
| J Hematol Oncol |
C3aR costimulation enhances the antitumor efficacy of CAR-T cell therapy through Th17 expansion and memory T cell induction. Mechanistically, BB- |
Direct oral anticoagulant versus low molecular weight heparin for the treatment of cancer-associated venous thromboembolism: 2022 updated systematic review and meta-analysis of randomized controlled trials. Six RCTs enrolling 3690 patients with CAT were included. Compared with LMWHs, DOACs significantly decreased the risk of CAT recurrence (RR, 0.67; 95%CI, 0.52-0.85), with a non-significant increase in the risk of major bleeding (RR, 1.17; 95%CI, 0.82-1.67), a significant increase in the risk of clinically relevant nonmajor bleeding (RR 1.66; 95%CI, 1.31-2.09) and no difference in all-cause mortality rates. These results increase the level of certainty of available evidence supporting the use of DOACs as an effective and safe option for the treatment of CAT in selected cancer patients. |
Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer. IL1RAP overexpression was associated with worse overall survival. IL1RAP knockdown significantly reduced cell viability, invasiveness, and clonogenic growth in pancreatic cancer cell lines. Inhibition of the downstream interleukin-1 receptor-associated kinase 4 (IRAK4) using two pharmacologic inhibitors, CA-4948 and PF06650833, resulted in reduced growth in pancreatic cancer cell lines and in xenograft models. |
Post-transplant cyclophosphamide alters immune signatures and leads to impaired T cell reconstitution in allogeneic hematopoietic stem cell transplant. Importantly, upregulation of PD-1 on CD8 T cells was persistent through day 180 and these T cells were less functional, manifested by reduced cytokine production upon anti-CD3/CD28 stimulation. Furthermore, we found a significant correlation of T cell immune phenotypes to clinical outcome (disease relapse and GVHD) in patients who received PTCy. Our novel findings provide critical information to understand the mechanism of how PTCy impacts immune reconstitution in allo-HSCT and may subsequently lead to optimization of our clinical practice using this treatment. |
Risk of SARS-CoV-2 Breakthrough Infection in Vaccinated Cancer Patients: A Retrospective Cohort Study. In order to better understand the risk of developing breakthrough SARS-CoV-2 infection and the outcomes associated with breakthrough infection for cancer patients, individual patient data from a curated outcomes database at the University of Kansas were retrospectively reviewed to determine the rate of breakthrough infection during an 8-month period encompassing the height of the delta variant surge. Although the rate of breakthrough infection in cancer patients after two doses of an mRNA vaccine remained low at 1.1%, hospitalization and death rates were 27 and 5%, respectively. Patients with hematologic malignancies, especially multiple myeloma, and those on anti-neoplastic therapy at the time of vaccination were found to be at higher risk for developing breakthrough infection. |
| Leukemia |
all remaining publications eg case reports, images of the month, etc…
| Blood |
| Blood Adv |
| Lancet Haematol |
| Leukemia |